UP-REGULATION OF ASTROCYTE-DERIVED TENASCIN-C CORRELATES WITH NEURITEOUTGROWTH IN THE RAT DENTATE GYRUS AFTER UNILATERAL ENTORHINAL CORTEXLESION

The extracellular matrix protein tenascin-C has been implicated in the regulation of axonal growth. Using unilateral entorhinal cortex lesio ns, which induce a massive sprouting response in the denervated outer molecular layer of the rat fascia dentata, the role of tenascin-C for axonal growth was investigated in vivo. Monoclonal antibodies against the neurite outgrowth and anti-adhesive domains of the molecule were e mployed. Immunostaining was increased throughout the denervated outer molecular layer by day 2, reached a maximum around day 10, and was bac k to control levels by four weeks post lesion. Growth cone deflecting as well as neurite outgrowth promoting isoforms of tenascin-C were up- regulated after the lesion. Using electron microscopy, single intensel y tenascin-C immunoreactive cells were identified as reactive astrocyt es that phagocytose degenerated terminals. In situ hybridization histo chemistry for tenascin-C messenger RNA revealed numerous cellular prof iles in the denervated outer molecular layer of the ipsilateral and co ntralateral dentate gyrus two days post lesion. Tenascin-C messenger R NA-positive cells in the outer molecular layer were identified as astr ocytes using double-labelling for tenascin-C messenger RNA and glial f ibrillary acidic protein immunohistochemistry. Thus, a tenascin-C-rich substrate is present in the outer molecular layer during the time of sprouting and a sharp boundary is formed against the inner molecular l ayer. This pattern may contribute to the layer-specific sprouting resp onse of surviving afferents after entorhinal lesion. Neurite outgrowth may be promoted within the denervated zone, whereas axons trying to g row into the denervated outer molecular layer, for example from the in ner molecular layer, would be deflected by a tenascin-C-rich barrier. (C) 1997 IBRO. Published by Elsevier Science Ltd.